Tanmay Lele, Ph.D., the Charles A. Stokes Professor of Chemical Engineering, has been awarded a National Institute of Health (NIH) U01 grant to examine the physical and molecular mechanisms of the cancer nucleus.
Research in the Lele Lab is focused on how the cell nucleus is shaped and positioned, and how these functions become abnormal in disease conditions. A recent discovery from the Lele Lab is that nuclei are shaped by mechanical stresses generated internally in cytoskeletal structures. These stresses are transmitted to the nucleus through cytoskeletal connections with proteins embedded in the nuclear membranes. These proteins are collectively referred to as the LINC complex, and many of them are mutated or abnormally expressed in cancer.
As part of this grant, Dr. Lele will lead a team of researchers who will study how alterations to the LINC complex can contribute to cancer development. They hypothesize that normal transmission of mechanical stresses by the LINC complex is necessary for cellular functions like migration and tissue formation, and that disruptions to the LINC complex may promote cell invasion and tissue dysfunction.
“The cancer nucleus remains highly understudied with much to learn about the physical principles that govern nuclear positioning, dysmorphia and chromatin organization, and how altered nuclear stresses contribute to cancer cell dysfunction,” Dr. Lele said.
Additional sites and study team members include Gregg G. Gundersen, Ph.D., at Columbia University; Richard B. Dickinson, Ph.D., at the University of Florida; Jonathan D. Licht, M.D., at the UF Health Cancer Center; and Jeffrey A. Nickerson, Ph.D., at University of Massachusetts Medical School, Worcester.
As the lead principal investigator in this U01 award, Dr. Lele will also serve in the Physical Sciences-Oncology Network (PS-ON) steering committee of the National Cancer Institute which is responsible for Network coordination and governance.
Dr. Lele is the director of the Institute of Cell & Tissue Science and Engineering at UF and has devoted his career to mechanobiology. He has been with the department since 2006 and continues to make strides in advancing the scientific understanding of how cells work. Dr. Lele holds an affiliate appointment in the J. Crayton Pruitt Family Department of Biomedical Engineering and Department of Mechanical & Aerospace Engineering.